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Objecves ● Recognize main divisions of and fungal Introducon to taxonomic groups. ● Idenfy various examples of herbals and associated organic compounds. ● Discuss main issues concerning herbal medicine Jason Schoneman MA, RN use in . The University of Texas at Ausn ● Examine current research surrounding medicinal

http://www.mexicolore.co.uk/aztecs/health .

Objecves ● Discuss history and role of psychedelic herbs in medicine and illness. ● List herbs used as legal and illicit drugs of Plantae abuse. ● Associate main plant and fungal families with representave poisonous compounds. ● Discuss clinical management of main toxic

http://scienceblogs.com/evolgen/2007/07/06/phylogeny- compounds. friday-06-july-2007/

Algae Bryophytes Brown algae Green algae Moss

http://ucommphoto.nmsu.edu http://en.wikipedia.org/wiki/Algae www.botany.ubc.ca/bryophyte

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Pteridophytes Ferns

Gymnosperms

Conifers Cycads Microcycas calocoma Cunninghamia sp. Taxodium distichum

Ginkgo Gnetophyta

Ginkgo biloba

Ephedra sinica

http://en.wikipedia.org/wiki/Ginkgo_biloba

http://en.wikipedia.org/wiki/Ephedra

2 4/17/14

Angiosperms Palms Monocots baileyana

Sedges Bananas Cladium sp. Musa sp.

Bromeliads Aroids Bromeliaceae Amorphophallus tanum

http://abrimaal.pro-e.pl/araceum/amorphophallus/titanum.htm

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Angiosperms Oaks Dicots Quercus sp.

Cac Hibiscus Hylocereus sp. Hibiscus coccineus

Pitcher plant Fungi Nepenthes sp.

http://sharonapbio-taxonomy.wikispaces.com/Fungi

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Main Groups of Fungi

● Zygomycetes (Bread molds) Ascomycetes ● Ascomycetes (Sac fungi) ● Basidiomycetes (Club fungi, “mushrooms”) Sac fungi

Aspergillus sp. Ergot fungi Claviceps purpurea

http://wpr.staff.ipb.ac.id/ http://en.wikipedia.org/wiki/Claviceps_purpurea

Morel Basidiomycetes Morchella sp. Club fungi

http://foragesouth.wordpress.com/tag/morel-mushrooms/

5 4/17/14

Fly agaric Panaeolus sp. Amanita muscaria

http://theergot.wordpress.com/2013/08/03/lets-get-excited-about- Schultes et al., 1992 shrooms/

Carbohydrates

● Cellulose (fiber) Main Organic Herbal ● Mycopolysaccharides: ○ Beta-glucans are the medicinal compounds in Compounds fungi and affect every area of the body.

Shitake Lennula edodes

China http://www.silversageherbs.com/zencart/index.php? main_page=product_info&products_id=334

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Lipids Lipids ● Fay acids (carbon chains with single carboxyl ● Alpha-linolenic acid (omega-3 polyunsaturated radical): ○ Palm fay acids): ○ ○ Flaxseed (Linum usitassimum) ● Gamma-linolenic acid (omega-6 polyunsaturated ● Hydrocarbon sulfides: fay acids): ○ Garlic (Allium savum) ○ Evening primrose (Oenethera binennis) ■ produces allicin with many medicinal values ○ Hemp (Cannabis sp.) ■ odiferous ○ Borage (Borago officinalis)

Omega-6

Olive Olea europaea

http://www.visionsmartcenter.com/information/16/GLA-Gamma%20Linolenic%20Acid

Evening Flaxseed primrose Linum usitassimum Oenethera binennis

http://www.ag.ndsu.edu/agnic/flax/wales%203.htm http://en.wikipedia.org/wiki/Oenothera

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Terpenes ● Aromac hydrocarbons: ○ backbone isoprene units (C5H8) Garlic ● Most numerous secondary plant compounds Allium savum ● Monoterpenes-essenal oils: ○ Lamiaceae (Mentha) ○ Pinaceae (Pinus) ○ Rutaceae (Citrus) http://tinyfarmblog.com/garlic-for-sale/

Terpenes ● Sesquiterpene lactones: ○ Artemesia annua ● Diterpenes: ○ Salvinorin A () ○ Ginkgolide A (Ginkgo biloba)

http://science.uvu.edu/ochem/index.php/alphabetical/s-t/terpenes/

Saponins

● Soap-like compounds (amphipathic glycosides) Artemesia ● Steroid saponins: Artemesia annua ○ Diosgenin (Dioscorea) ■ precursor for progesterone formaon ○ Ginsenoside Re (Panax ginseng)

http://www.mswn.com/plants/database/plant/artemisia-frigida/

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Saponins ● Cardiac glycosides: ○ Oleander (Nerium) ○ Foxglove (Digitalis sp.) ● Tetraterpeniods: ○ carotenes ○ xanthophylls

○ renoids https://www.standardprocess.com/Products/MediHerb/Wild-Yam-12 ○ colors=anoxidants

Wild Yam Dioscorea sp. Foxglove Digitalis purpurea

http://www.cnseed.org/purple-foxglove-digitalis-purpurea.html https://www.standardprocess.com/Products/MediHerb/Wild-Yam-12

Polyphenols Polyphenols ● Quinones: ● Made up of mulple phenol types ○ Sennoside A (Senna alexandrina) ○ (C6H5OH)-aromac benzene ring ○ Hypericin ● Simple phenols and phenolic acids: ■ (“St. John’s Wort”Hypericum perforatum) ○ Salicin (Salix sp.) ● Slbenoids: ○ Delta-9-tetracannabinol (Cannabis sp.) ○ Resveratrol (Vis vinifera) ○ Vanillin (Vanilla planifolia) ● Flavonoids: ○ anthocyanins=colors=anoxidants

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Willow Salix sp.

http://www.mdidea.net/products/herbextract/salicin/data02.html

http://en.wikipedia.org/wiki/Salix_alba

Senna Vanilla Senna alexandrina Vanilla planifolia

http://botanical.com/botanical/mgmh/s/senna-42.html

● : Alkaloids ● Purine: ○ Tobacco (Nicoana sp.) ○ Methylxanthines ● B-carboline: ■ Caffeine: Coffea, Ilex paraguariensis, Cola ○ Harmaline (Passiflora sp.) acuminata ○ Mescaline (Lophophora, Echinopsis) ■ Caffeine, theobromine: Theobroma cacao ○ Muscimol (Amanita muscaria) ■ Caffeine, theophylline: Camellia sinensis ○ Psilocybin (“magic mushrooms”) ● Isoquinoline: ○ Vinblasne and Vincrisne (Catharanthus ○ , codeine (Papaver somniferum) roseus–Madagascar periwinkle)

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Alkaloids Alkaloids ● Indole: ● Tropane (ancholinergics): ○ Ergot (Claviceps sp.) ○ ,, (Atropa ○ d-cathine (Catha edulis) belladonna, Datura, Brugmansia, Mandragora ○ l-ephedrine, d-pseudoephedrine (Ephedra sp.) officinarum) ● Quinoline: ○ Tubocurare (Chondrodendron tomentosum) ○ Quinine (Cinchona officinalis) ○ & (Erythroxylum coca) ● Taxol (Taxus sp.)

http://waynesword.palomar.edu/ww0703.htm http://en.wikipedia.org/wiki/Autonomic_nervous_system

Tobacco Nicoana tabacum

http://en.wikipedia.org/wiki/Autonomic_nervous_system

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Fly agaric Amanita muscaria

http://en.wikipedia.org/nervous_system

Madagascar Curare periwinkle Chondrodendron Catharanthus roseus tomentosum

http://commons.wikimedia.org/wiki/ File:Starr_070906-8657_Catharanthus_roseus.jpg

http://www.cindysantiqueart.com/print-Chondrodendron

Tea Coffee Camellia sinensis Coffea arabica Cocoa Theobroma cacao

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Jimson Weed Angels Trumpet Datura sp. Brugmansia sp. poppy Papaver somniferum

http://www.aaronhuey.com/#/editorial-archive/afghanistan-drug-war/ Opium_032

Mandrake Coca Mandragora Erythroxylum coca officinarum

http://ignorf.net/what_is_a_mandrake.htm

Quinine Taxol Cinchona officinalis Taxus sp.

http://en.wikipedia.org/wiki/Cinchona http://commons.wikimedia.org/wiki/ File:Illustration_Taxus_baccata0.jpg

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Holisc Medicine

Herbal Medicine

http://www.myballard.com/wp-content/uploads/health-fair.jpg

“Herb” Herbal History ● Plant, fungus, animal, or mineral ● Medicinal plant use predates recorded history ● Graves of Neanderthal: 60K y/o ● From gentle tonics to deadly toxins ● Oral transmission of knowledge

Herbal History Herbal History ● Sumerian drawings: 2500 B.P. ● Golden Age of Greece: 400 B.P. to 90 A.P. ● Tablets from Babylon empire: ~1700 B.P. ○ Aristotle (menons henbane, licorice, and mint) ○ (first descripon opium effects) ● Egypans: temple walls and Ebers Papyrus record ○ Dioscorides () over 700 medicinal formulas ○ Nicander (book of poisons)

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Herbal History ● Middle ages: Monks compiled and copied Greek texts and local knowledge into herbals Persian Walnut ● Badianus manuscript ● Renaissance: Paracelsus rejected previous Juglans regia knowledge and invented his “doctrine of signatures”

http://en.wikipedia.org/wiki/File:Whole_Walnut_Kernel.jpg

“For the shaman or indigenous insider, a parcular plant’s Herbal History chemistry, phenology, community associates, habitat, uses, cultural value, mythic associaons, growth curve, physical • Majority of discoveries from knowledge of rural- properes and usual management come to mind in a living and indigenous peoples constellaon of associated knowledge whenever the plant or its name is encountered in walking, thought, or conversaon.” • 19th century to present: Janis Alcorn p. 25. o creaon of drugs via extracon Ethnobotany: o semi-synthesis of herbal compounds and Evoluon of a analogs Discipline

http://www.environmentalgraffiti.com/news-kayapo-people-get-helping-hand

Types of Herbalism Types of Herbalism ● Indigenous ● European ○ Most diverse ○ Roots from ancient Egypan ○ Orally transmied via shamanic knowledge ○ Ferle Crescent ● Chinese (Wu-Sing) ○ Mediterranean civilizaons ● Indian: (Hindu), Unani (Islamic) ● Neo-Western ● Japanese () ○ Fuses Indigenous, European and Asian herbalism

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http://djcadchina.wordpress.com/2012/02/page/16/

http://www.flickriver.com/photos/tags/unani/interesting/ http://nabatawy.blog.com/2010/04/09/egyptian-plants/

From Forest to Market ● Ethnobotany ○ Threatened cultures ○ Threatened species ■ Currently 5000X greater than natural rate ■ Climate change, polluon, invasive species, habitat loss ■ Data: taxonomic, plant part, site, habitat, http://www.waltshealthfoods.com/products.html method of preparaon, etc.

16

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Screening Programs ● Pharmacognosy ○ Study of physical, chemical, biochemical and biological properes of drugs and search for drugs from natural substances ○ Screening programs ○ Separaon, idenficaon and acvity: ■ Chromatography, Spectroscopy ■ Bioassays

http://faculty.sdmiramar.edu/fgarces/LabMatters/Instruments/Chromatography/ Chromatography.htm

Herbals in United States FDA Standards ● ~40% of Americans now use some form of ● Dietary Supplement Health and Educaon Act complementary and alternave medicine (CAM) (DSHEA) of 1994 ● ~5 billion dollars in revenue/year in US, ~60 billion

worldwide ● “Herbals” classified as supplements and foods ● Soaring healthcare costs, prophylaccs, last resort, ● No FDA approval needed before producon and less invasive, less dangerous distribuon ● U.S. pts. fail to disclose use due to: HCP disinterest, ● Safe unl proven otherwise HCP negave response or lack of knowledge

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FDA Standards FDA Standards ● Labeling: ● Good Manufacturing Pracces (GMP) ○ Safety and truthfulness ● Europe ○ No known efficacy ○ Germany ○ Can discuss “structure funcon claims” ■ Follows Commission E monographs (do not need extensive supporve evidence) ■ Rest of Europe following lead of Germany ● USP (US Pharmacopoeia) and NF (Naonal ● Asia Formulary): ○ Minimal regulaons ○ determine quality of herbals

Quality Issues ● Contaminaon/Adulteraon ○ Mistaken plants ○ Substuon of related species ○ Mycotoxins ○ Pescides

Newmaster et al., 2013

Quality Issues ● Radioacve ○ Cadmium ● Heavy metals ○ Lead ○ Arsenic (rice, , vegetables) ○ Thallium ● Environmental polluon Newmaster et al., 2013 ○ Salmonella

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Clinical Issues Harvest, Storage, & Producon ● Allergic reacons ● Issues: ● Mutagenic effects ○ Genec variability ● Drug-drug interacons ○ Growth condions ● Contraindicaons: not enough data ○ Time of harvest ● Adverse/Side effects ○ Stage of growth ○ Length of storage ○ Storage condions ○ Binders, fillers used in packaging

Research Issues

● Plant misidenficaon ● Product contaminaon 5 Herbs to Know ● Inadequate analyses for acve compounds ● Lack of pharmacokinec and pharmacodynamic informaon ● Need more prospecve, randomized, placebo- controlled, blinded, and mulcenter studies

Black Cohosh Black Cohosh

● Actaea racemosa (Ranunculaceae)-rale snake ● ADRs: root ○ Hepatotoxicity ● Taken for menopause symptoms and ○ GI irritability dysmenorrhea ○ Rash ● Efficacy not research supported ● Drug-drug interacons ○ CYP 3A4 inhibion ○ Chemotherapeuc agents

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Acai

● Euterpe oleraceae ()-Acai berry ● Taken for HLD, allergies and cancer ● Moderate support for immune modulang effects and providing protecon against ROS and inflammaon (high concentraon of anthocyanins)

http://williambritten.com/wordpress/wildflowers/smoky-mountains-wildflowers-black-cohosh/

Acai ● ADRs: ○ None known ● Drug-drug interacons: ○ None known ● Precauons: ○ Chagas disease

http://nutrivize.com/blog/general-health/acai-superfruit-or-superscam/

Ginkgo Ginkgo

● Ginkgo biloba (Ginkgoaceae)-fossil ● ADRs:

● Taken for infecon, cancer and cognive decline ○ Seizure

● Research is conflicng in supporng its efficacy and ○ Spontaneous bleeding

the recent large GEM study does not support its ● Drug-drug interacons

use in minimizing cognive decline ○ An-seizure agents ○ Ancoagulants/anplatelets ○ MOAIs

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Milk Thistle ● Silybum marianum (Asteraceae)-Holy thistle ● Taken for liver disease ● Research supports its effecveness in reducing aminotransferases in ETOH cirrhosis. Support for its use against other liver diseases is weak ● ADRs: Transaminis in high doses ● Drug-drug interacons

http://fr.wikipedia.org/wiki/Ginkgo_biloba ○ strong CYP 3A4 inhibitor

St. Johns Wort ● Hypericum perforatum (Hypericaceae)-witches herb ● Taken for anxiety, depression, sleep and neuropathic pain ● Contraindicaons: ○ pregnancy ○ taking any other andepressants (serotonin syndrome) http://en.wikipedia.org/wiki/File:Milk_thistle_flowerhead.jpg

St. Johns Wort St. Johns Wort ● ADRs: ● Research supports its effecveness (as effecve ○ photosensivity as most SSRIs) against mild to moderate ○ N/V depression (reuptake inhibitor of serotonin, ○ GI irritability ○ coagulopathy norepinephrine and dopamine) ○ sexual dysfuncon ○ disconnuaon syndrome ● Drug-drug interacons ○ strong CYP 3A4 inducon and many other drugs!

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Herbal Resources National Center for Complementary and http://nccam.nih.gov/health/ supplements.htn http://nccam.nih.gov/index.htm

Office of Dietary Supplements http://ods.od.nih.gov/

Natural Medicine Comprehensive www.naturaldatabase.com Database

Natural Standard www.naturalstandard.com

Consumer Labs http://www.consumerlab/results/index.asp

Memorial Sloan Kettering Center www.mskcc.org/aboutherbs Integrative Medicine Smart phone/Tablet application: About Herbs http://en.wikipedia.org/wiki/St_John's_wort

Herbal Resources Cochrane Library’s field group in http://www.cochranelibrary.com Medicinal Cannabis CAM website

Food and Drug Administration www.fda.gov/Food/ DietarySupplements/default.htm

MedWatch www.fda.gov/Safety/MedWatch/ default.htm

American Botanical Council http://www.herbmed.org/ http://www.herbalgram.org

US Pharmacopeia http://www.usp.org

http://www.thedailychronic.net/2013/18294/the-starbucks

History “Very few drugs, if any, have such a tangled history as a medicine. In fact, prejudice, ● Use started in Central Asia with proto-Indo superson, emoonalism, and even ideology Europeans (Kurgans in ancient “Romania”) ● Later to West Asia (Scythians, Hebrews) and to have managed to lead cannabis to ups and India and China downs concerning both its therapeuc ● Chinese shamans; Chinese emperor Shen Nung properes and its toxicological and dependence- prescribed 5k years ago inducing effects.” E. A. Carlini

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History History ● Greeks (Hippocrates) , Romans (), Norse ● Path towards illegal status ● India: Sadhus ○ Harry Anslinger and the Federal Bureau of ● Used as curave by Irish immigrants physicians in Narcocs: Reefer Madness and Marihuana Tax th late 19 century U.S of 1937 ● Before 1960s used mainly by European ○ Taken out of US pharmacopoeia and NF in 1941 st intellectuals, 1 generaon Hispanics and African ○ Outlawed in 1971 (Controlled Substance Act) Americans

Cannabis sava

http://en.wikipedia.org/wiki/ http://www.photoburst.net/travel-photography/2013/05/babughat-kolkata File:Cannabis_sativa_Koehler_drawing.jpg

Hashish

Cannabis indica

http://ganjavibes.wordpress.com/tag/indica/

http://www.cannabissativa.com/cannabis/

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Cannabinoids Cannabinoid Receptors

● ~70 phytocannabinoids ● Classical: ● Endogenous: ○ CB1-THC ○ Human receptor system-anandamide and 2- ● Nonclassical: AG ○ CB2: majority of other cannabinoids ● Synthec

Synthecs Extracts ● Dronabinol (Marinol): ● Nabiximols (Savex): ○ N/V for Ca chemo, appete smulant for AIDS ○ Mouth spray with 1:1 rao of CB1:CB2 from cachexia cannabis ○ Schedule III ○ Europe and only ● Nabilone (Cesamet): ○ In phase 3 trials in US: neuropathic pain

○ N/V, neuropathic pain, MS, fibromyalgia ● Epidiolex: ○ Cannabidiol extract for treatment of Lennox- ○ Schedule II: more potent than Marinol Gastaut syndrome(LGS)

Use Risks Use Risks ● Most widely used illicit drug in the world: over ● Cannabis dependence syndrome: 200 million regular users ○ psychological addicon (1 in 10 users) ● Cognive developmental delays if started before ○ IOM probability of dependence: age 18 and used chronically for ~10 years ■ MJ (9%) ● Increasing rates of THC: ■ ETOH (18%), ○ MJ: 5-35% ■ Cocaine (17%), ○ Hashish: 5-20% ■ Opiates (23%), ○ Hash oil: 15-60% ■ Nicone (32%)

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Use Risks Use Risks ● Same gateway drug risks as ETOH ● Lung cancer ● Idiosyncrac sensivity to CB1 ● Chronic bronchis with long term chronic use ● Contraindicated: Family hx or hx of personality ● Contaminants: disorders or psychosis ○ Aspergillus and bacteria ● Strict precauons in: ○ Heavy metals ○ Pregnant of breast feeding women ○ Organophosphates ○ <18 y/o ○ Adulterants: PCP, cocaine, methamphetamine, ○ Elderly heroin, opium, sedaves, formalin ○ Substance abuse hx

Use Risks Use Benefits ● No toxic dose: ○ possible therapeuc rao of 50K X (lithium and ● Neuropathic and Chronic pain digoxin 2-3 X) ● ALS/End of life ● Withdrawal symptoms: ● Decreases muscle spascity in MS ○ relavely mild ● Levodopa induced dyskinesia in Parkinsons ● Minimal drug-drug interacons: ○ CYP2C metabolism ● Criminal record and incarceraon

Use Benefits Use Benefits ● Cachexia ● PTSD ● Preliminary data: ■ IBS & IBD ● Tics in Touree syndrome ■ Glaucoma ■ Migraines ● N/V ■ Anepilepc ■ Ancancer (CBD, CBG, CBGV) ■ Alzheimers ■ Fibromyalgia

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Future Research Federal and State Law ● Schedule I drug: ● MDD ○ High abuse potenal, no medical use, lack of ● Demena drugs accepted safety with MD supervision, other ● Bronchodilators drugs in this schedule: , heroin ● Anallergen ● Schedule II: morphine, PCP, cocaine, , ● Anpsychocs methamphetamine

Federal and State Law Federal and State Law

● Many researchers and healthcare professionals in ● Benchmark data for schedule II approval exists: US requesng Cannabis transfer to schedule II or ○ Therapeuc and palliave effects equivalent to allow access to schedule I for research other drugs ○ NAS, IOM, NIH, AMA, ACP vs. DEA, FDA, SAMHSA, NIDA ● Current state legislaon allows medicinal Cannabis for almost any indicaon with minimal oversight

http://www.motherjones.com/politics/2014/02/pot-marijuana-legalization-map-states

http://psychotropia.co/?cat=12

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Psychedelics History ● Shamanic divinaon/ritual Sacraments: spiritual tools or sacred medicine by ○ Soma: proto-Indo Europeans non-Western cultures ○ Smulus for religion: vs. ■ Eleusinian Rites Dangerous drugs of abuse ● Ergot poisoning vs. ○ St. Anthony’s Fire Research and clinical tools for mental and physical ○ Salem Witch Trials disorders

History Main Groups Tryptamines LSD, Psilocybin, DMT, ● Psychotherapy

○ 20th century: unl 1971 ● Recreaonal Phenethylamines MDMA, Mescaline, Myristicin ○ Smulus of U.S. cultural revoluon Dissociative Ketamine, Phencyclidine hallucinogens (PCP), Ibogaine, Salvia

Main Groups Lysergic Acid Diethylamide (LSD) Other , Fly agaric ● Ergot fungus (Claviceps purpurea ) ● Potent 5HT agonist 2A ● Colorless, odorless, tasteless and the most Pseudo- Cannabis potent drug known on the planet ○ 20 mcg can alter consciousness for 12 hours Anticholinergics Tropanes

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Lysergic Acid Diethylamide (LSD)

● Avoid in pre-exisng mental illness, parcularly schizophrenia ● Psychotherapy for anxiety based disorders Ergot fungus (mainly end of life (cancer)) and addicons Claviceps purpurea ● Cluster headaches

http://en.wikipedia.org/wiki/Claviceps_purpurea

Psilocybin Psilocybe cubensis ● Converted to Psilocin in body ● Found in many species of mushrooms

● 5HT2A agonist ● Psychotherapy ○ OCD ○ End of life anxiety (cancer) ○ MDD ○ Nicone addicon

● Cluster headaches http://divawhispers.com/onthescene/

N, N Dimethyltryptamine (DMT) ● Endogenous compound in humans ○ In near death experiences, DMT secreted from pineal gland ● Virola (Epena), Anadenanthera (Yopo), Psychotria, Bufo alvarius

● 5HT2A agonist ● Broken down by monoamine oxidases, so needs

MAOI adjunct or bypass MAOIs http://www.amazon-indians.org/yanomami.html

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Ibogaine ● iboga ()

● 5HT2A agonist, NMDA receptor antagonist, kappa receptor agonist ● Psychotherapy ○ An-addicon: ETOH, cocaine, opiates/

Schultes et al., 1992

Mescaline ● From various species of cac

● 5HT2A agonist, adrenergic, dopaminergic ● Psychotherapy ○ Addicons

Schultes et al., 1992

MDMA (Ecstasy) ● Synthesized from various plant precursors ● 5HT1A, 5HT1B, 5HT2A agonist, adrenergic, Peyote dopaminergic Lophophora ● Psychotherapy williamsii ○ PTSD ○ MDD (ECT replacement)

http://fineartamerica.com/featured/close-view-of-peyote-cacti-lophophorus-ira-block.html ○ Borderline personality disorder

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Ayahuasca ● Mixture of two known hallucinogenic plants and many other admixture plants ● Bansteriopsis caapi: Beta carboline harmala alkaloids and MAOIs ● Psychotria viridis (Rubiaceae): DMT but needing MAOI to be acvated orally ● Ayahuasca churches

http://www.redcloudindianarts.com/e-luna3.htm

Natural and Semi- Synthec Legal Highs ● Natural: not yet on radar of public and legislave bodies ● Synthec: The Controlled Substance Analogue Enforcement Act of 1986, tacked on to Controlled Substances Act of 1971: ○ chemical structure must be structurally similar

http://www.telegraph.co.uk/news/picturegalleries to other class I or IIs or acts same physiologically

Overdose Management Synthec Cannabinoids ● Supporve therapy ● ‘Spice’ and many other common names ● BZDs: mainly Avan ○ Compounds synthesized and sprayed on inert ● Restraints? plant material and sold as incense to bypass ● Lab and diagnosc tests: detecon or legal scruny ○ CBC, CMP, Tox screen, Cardiac , ECG, ● Over 400 compounds from work of Dr. Huffman EEG (creaon of cannabinoids for research) ● 2nd most abused recreaonal drug behind Cannabis:

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Synthec Cannabinoids

● Can bypass drug tests: used by law, fire and armed forces ● Many mes more potent than hash oil ● Has been associated with psychosis, seizures, and MIs ● Treatment ○ BZDs and Trazodone http://winnipeg.ctvnews.ca/winnipeggers

Salvia Salvia ● Salvia divinorum (Lamiaceae) ● Used at greater rate than ecstasy in 18-24 y/o ● Ancient Mazatec herb for shamanic divinaon ● Smoked ● Kappa opioid receptor agonist, dopaminergic ● Has been associated with anxiety and psychosis ● Kept from schedule I status: ● Treatment: ○ due to being promising candidate for novel ○ BZDs andepressant and non-addicve analgesics and anesthecs

Methedione/Methylone ● Synthec derivaves of Cathinone found in Khat (Catha edulis) ○ nave to East Africa and Arabian peninsula and chewed for millennia for amphetamine-like qualies ● Known as “bath salts” ● Potent adrenergic and MAOI

http://en.wikipedia.org/wiki/File:Salvia_Divinorum ● Snorted and injected

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Methedione/Methylone ● Causes: ○ agitaon ○ seizures ○ excessive sympathomimec smulaon: ■ tachycardia, confusion, psychosis, hyponatremia ● Treatment

○ BZDs http://www.jewishjournal.com/world/article/widespread_khat_addiction_threatens_yemens_future

Ancholinergics ● Datura, Brugmansia, Belladonna, Henbane ● Causes: ○ Tachycardia, HTN, restlessness, delirium, blurred vision ○ Hallucinaons: auditory, visual ● Treatment ○ Acetylcholinesterase inhibitor: ■ Physosgmine

http://fauxsociety.com/bath-salts-and-the-taste-for-flesh-zombie/

Cholinergics: Isoxazoles ● Occur in the genera: Clitocybe, Inocybe and in two species of Amanita ● Muscimol: GABA agonist, seratogenic, dopiminergic ● Ibotenic acid: NMDA agonist ● Fatalies rare but possible to die with ingeson of 10 or more mushrooms ● Treatment: supporve

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Other Legal Highs ● Kratom (Mitragyna speciosa) ○ Mitragynine: adrenerigic, mu and kappa opioid agonist, NMDA antagonist, seratonergic ● Morning glory (Ipomoea violacea) ○ LSA (d-lysergic acid amide): potent seratonergic

http://en.wikipedia.org/wiki/List_of_Amanita_species

Other Legal Highs ● Betel nut (Areca catechu) ○ Arecaidine and arecoline: adrenergic, GABA inhibitor, cholinergic agonist, highly carcinogenic ● Nutmeg (Myrisca fragrans) ○ Myrisn (MAOI): adrenergic, dopiminergic, seratonergic

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Herbal Poisons Herbal Poisons ● Acute management of poisoning ● Gastric decontaminaon ○ Immediate stabilizaon, decontaminaon, ○ Ipecac: no longer recommended exam and labs ○ Gastric lavage: no longer recommended ○ Pay close aenon to toxidrome, physical ○ Whole bowel irrigaon: not recommended in and verbal evidence for source of poisoning herbal poisoning ○ Labs: CBC, CMP, UA, Coags, ECG, Cardiac ○ Charcoal: case by case basis, and only if can enzymes, ABGs, Tox screen, EEG be administered in first 1-2 hours of herbal ingeson

Algae ● Pfiesteria piscicida (dinoflagellate): toxin 1000 mes stronger than cyanide, AKA “fish Ebola”, indirect via shellfish ● Signs and symptoms: fague, arthralgias, paresthesias, nausea, open sores, memory loss (lasng 1-2 weeks aer exposure), disorientaon ● Treatment ○ Supporve de.wikipedia.org/ wiki/Pfiesteria_piscicida

Pteridophytes ● Pteridium aquilinum: ○ Bracken fern ● Carcinogenic ptaquiloside and thiaminase: ○ neoplasms of the upper alimentary tract ●Found throughout east Texas and the mountains of west Texas ● Treatment: ○ Prevenon

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Gymnosperms Gymnosperms ● Cycadaceae: primarily Cycas revoluta (“Sago ● Texas ornamental palm”) in Texas. ● Signs and symptoms: ● Palm-like pinnate leaves, but disnct cone-like ○ icterus, jaundice, N/V, liver failure, reproducve structures weakness, seizures ● Neurodegenerave azoxy glycosides and ● Treatment: mutagenic cycasin ○ Supporve

Ephedra ● Ephedra sp. (joinirs, ma huang, mormon tea) ○ thin ○ oen light green to blue ○ jointed stems with small cone-like reproducve structures ● Natural source of ephedrine and d- pseudoephedrine

Ephedra ● Distribuon is widespread in drier regions of the world, occurs in west Texas ● Signs and symptoms: ○ headache, diaphoresis, hyperthermia, MI/ Stroke, seizures, agitaon ● Treatment: ○ BZDs http://commons.wikimedia.org/wiki/ File:Ephedra_fragilis_3.JPG

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Araceae ● Araceae (Anthurium, Arisaema (Jack-in-the-pulpit), Arum (Lords and Ladies), Caladium, Colocasia, Angiosperms Dieffenbachia, Monstera, Alocasia, Philodendron) ● Raphides (cells) contain calcium oxalate crystals in Monocots the shape of needles and proteolyc enzymes in some genera ● Extremely diverse leaf morphology but generally similar reproducve structures (spathe and spadix)

Araceae ● Alocasia, Colocasia (Taro), and Xanthosoma eaten throughout Asia and South Pacific, some variees with significant raphides ● Signs and symptoms: edema, erythema, bullae, altered speech, laryngeal occlusion ● Treatment: ○ Removal ○ Anhistamines

○ Steroids www.meemelink.com www.sarracenia.com/

Liliaceae ● Colchicum (Autumn crocus), Convallaria (Lily-of-the- valley), Gloriosa simplex (Gloriosa lily), Narcissus (daffodil, narcissus), Tulipa (tulip), Hymenocallis (spider lily), Amyrillis (naked ladies, etc.) ● Grass-like parallel veined leaves and trimerous (flower parts in threes), showy flowers; underground stems (e.g. bulbs and corms) ● A few uncommon nave species, mainly ornamental

http://forums2.gardenweb.com/forums/load/houseplt genera are problemac

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Liliaceae ● Toxins include: colchicine (highest in corms and seeds), lycorine, cardiac glycosides ● Signs and symptoms: fever, leukocytosis, palpitaons, dysrhythmias, shortness of breath, N/ V, abdominal pain, diarrhea, hematuria, dizziness, MODS ● Treatment: ○ Atropine ○ Fab fragment angen binding

Solanaceae ● (deadly nightshade), Datura (jimsonweed), Hyoscamus (henbane), Lycopersicon Angiosperms esculentum (tomato), *Nicoana (tobacco), Solanum (black nightshade, horse nele, potato, etc.), Dicots Brugmansia (angel trumpet) ● Diverse leave and stem morphology, flowers usually funnel-shaped and fused and fused stamens ● Toxic tropane alkaloids: hyoscyamine, atropine, scopolamine, solanine, cocaine

Solanaceae ● Nave Solanum and Datura, others introduced or for food, smoke and ornamentals ● Signs and symptoms: dry mucous membranes, blurred vision, hyperthermia, HTN, tachycardia, ileus, urinary retenon, agitaon, hallucinaons, delirium, seizures ● Treatment ○ Supporve ○ BZDs for cocaine ○ Physosgmine for tropanes

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Schultes et al., 1992

Anacardiaceae ● Toxicodendron (radicans=poison ivy, diversilobium and quercifolium=western and eastern poison oak respecvely, vernix=poison sumac) Mangifera (mango), Anacardium (cashew) ● Small viny to tall , resinous leaves and bark, finely divided leaves (pinnately compound) ● Toxic compound: oleoresin (urushiol)

wikipedia/commons/a/a0/Illustration_Atropa

Anacardiaceae ● Signs and symptoms: type I hypersensivity- extreme pruris and pain, erythrema, vesicles- bullae ● Treatment: ○ removal: soap and water ○ anhistamines ○ analgesics ○ Zanfel, calamine, oatmeal baths

○ Severe cases: systemic or topical steroids aloneonalimb.blogspot.com

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aloneonalimb.blogspot.com

http://en.wikipedia.org/wiki/Cashew

Apocynaceae Apocynaceae ● Adenium (desert rose), Asclepias (milkweed), Nerium ● Asclepias represented in Texas; other genera listed (oleander), Thevea (yellow oleander), Catharanthus above grown as ornamentals roseus (rosy periwinkle) ● Signs and symptoms: anorexia, headache, ● oen fused as a tube and showy; all parts of photophobia, blurred vision, dysrhythmias, plant (flowers not always) exude white latex when dizziness, palpitaons, shortness of breath, MI/ torn or broken stroke, N/V, abdominal pain, seizures, delirium ● Cardiac glycosides ● Treatment: ○ Digitalis (digoxin and digitoxin) ○ Atropine ○ Liliaceae ○ Fab fragment angen binding

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http://commons.wikimedia.org/wiki/File:Starr_070906-8657_Catharanthus_roseus.jpg

Fabaceae ● Abrus precatorius (rosary pea), Acacia, Albizia, Astralagus (locoweeds), Erythrina (coral bean), Lupinus (bluebonnet, lupine), Physosgma (Calabar or ordeal bean), Sophora secundiflora (mescal bean, Texas mountain laurel), Wisteria ● Leaves oen pinnately compound, flowers showy, fruits are always legumes ● Cyanogenic glycosides, cyssine, physosgmine, quinolizidines, curare-like alkaloids, locaine, erythrane, http://www.taiwanplant.com/finishedplants_desert_rose.htm coralline

Fabaceae ● Many of these genera found growing in Texas either as endemics, ornamentals, or in an agricultural seng ● Signs and symptoms: fever, blurred vision, diaphoresis, excessive salivaon, bradycardia, shortness of breath, bronchospasm, N/V, dizziness, muscle spasm, abnormal gait, seizures ● Treatment: ○ Supporve

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http://www.erowid.org/

Euphorbiaceae ● Croton, Euphorbia, Manihot esculenta (cassava, yuca), Ricinis communis (castor bean) ● Cac-like, large trees to minute prostrate herbs, flowers with nectar glands, white latex with cellular damage ● Ricin, amygdalin and linamian=HCN, cytotoxic diterpenes ● Type I and IV hypersensivity: latex angens (prohevein), mostly from Rubber tree (Hevea brasiliensis)

Euphorbiaceae ● Signs and symptoms: ○ Ricin: resp. distress, hypotension, bloody urine and stool (36-72hrs unl death) ○ HCN: headache, blindness, deafness, dizziness, shortness of breath, N/V, diarrhea, inebriaon, seizures, loss of sensorium

● Treatment: http://www.unitedfarmersassociation.com

○ HCN-hydroxocobalamin to form B12 (cyanobalamin), nitrites and thiosulfates ○ Ricin-Supporve

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http://en.wikipedia.org/wiki/Castor_oil_plant

Apiaceae ● Aethusa spp. (fools parsley), Cicuta maculata (water hemlock), (poison hemlock) ● Small to large herbs, the inflorescence of flowers arranged in an umbel ● Poisonous alkaloids, cicutoxin, coniine, resins; especially poisonous are leaves, unripe fruits and roots

http://www.myessentia.com/blog/why-natural-hevea-rubber-is- awesome/

Apiaceae ● Poison hemlock nave to Texas, the rest are found elsewhere in N. America ● Phytophotodermas: fucocoumarins ● Signs and symptoms: tachycardia to bradycardia, hypotension, N/V, abd pain, severe seizures, shock, coma, death ● Treatment: ○ Supporve

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Others ● Rosaceae: ○ Prunus spp. (apricots, plums, bier almonds, peach, and black cherry) and Pyrus spp. (pear) ○ Contain amygdalin which hydrolyzes into HCN ■ occurs in seeds, leaves, and bark, but most highly concentrated in seeds

http://www.skinps.com/blog/category/skin-conditions/

Others ● Order Ranunculales: ○ Includes Ranunculaceae and Papaveraceae ■ Aconum (monkshood), Anemone, Aquilegia (columbine), Argemone (prickly poppy), Clemas, Delphinium (larkspur), Papaver (poppies) ○ All of which mostly have toxic alkaloids

http://images.google.com/imgres?imgurl http://www.biology-blog.com/imag/columbine

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http://www.burma-all.com/new%20burma http://ipcblog.org/2011/09/06/mother-natures-most-toxic/

Case Study ● 38 y/o female presenng with N/V, severe abd. pain, conspaon alternang with diarrhea; 6 similar episodes in last year all requiring ED visits, Mycotoxins only tramadol effecve in pain management ● No PMH ● Lives on farm and all protein needs met from farm animals

Case Study Environmental/Food-related ● Repeatedly (-): CBC, CMP, amylase, lipase, abd. ● Aflatoxins US, stool exam with O&P, tTG, Hepas A,B,C, ● Ochratoxin hCG, UA, FIT, ECG ● Citrinin ● Only significant findings: (+) ESR, colonoscopy: ● Patulin areas of inflammaon without any ulceraon ● Fusarium ● Subsequent invesgaon revealed highly elevated AFB1 levels in farm animals, strong evidence supporng aflatoxicosis as eology

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Case Study ● 55 y/o woman and her daughters collected wild mushrooms for soup and ate it with son and grandaughter ● Within 12 hours all experienced N/V, abd cramping, diarrhea ● All were treated for diarrhea with fluid resuscitaon ● The children all died of fulminant hepac and renal failure within the next few days ● The mother survived aer 4 weeks of intensive

http://en.wikipedia.org/wiki/File:Aspergillus_on_tomato.jpg supporve care

Cyclopepdes ● Occur in the genus Amanita ● Amatoxin: alpha-amanin ● Inhibits protein synthesis in hepatocytes and causes nephrotoxicity ● Can not be deacvated by heat ● Cause ~90% of all fungi poisoning deaths and ~30% of individuals with cyclopepde poisoning

die http://en.wikipedia.org/wiki/Amanita_phalloides

Case Study Case Study ● 49 y/o Korean female presented to ED with GI ● Labs: LDH-243, Total bili-63 irritability and voming, D/C aer symptomac ● Symptomac treatment and IV pyridoxine treatment, returned with interpreter next day to administered inform and give example of wild mushrooms ● For 4 more days: pt. with lethargy, abd. pain, ean, pt with intense abd. pain, voming and anorexia, N/V; Labs on day 5: LDH-693, AST-431, chills ALT-472 ● PE: vitals WNL, abd. tenderness, rare bowel ● Eventual full recovery sounds

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-Hydrazine ● Occur in Gyromitra spp. (false morels) ● Monomethylhydrazine ● Can be inacvated with heat but volalizaon during cooking process can cause poisoning ● Similar to Isoniazid toxicity, as it causes B6 (pyridoxine) depleon which stops GABA synthesis ● Fatalies occur ~10% of the me

http://en.wikipedia.org/wiki/File:Frühjahrslorchel.JPG

Coprine ● Occur in Coprinus spp. (inky caps) ● Disulfirum-like reacon-hyperacetaldehydemia with ETOH ● Can not be inacvated with heat

http://www.mushroomexpert.com/images/kuo/coprinus_micaceus_06big.jpg

Orelline+Orellanine ● Occur in Cornarius spp. ● Disrupt the cytoskeleton and protein synthesis in renal tubular cells ● Can not be inacvated with heat

http://www.mushroomexpert.com/cortinarius_iodes.html

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Herbals: Resources Resources Cannabis: Ashar, B., Rowland-Seymour, A. (2008). Advising paent who use dietary supplements. The American Journal of Medicine, 121(2), 91-97. Abrams, D., Jay, C. & Shade, S. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo controlled trial. Neurology, 68, 515-521. Chan, K. (2003). Some aspects of toxic contaminants in herbal medicines. Chemosphere, 52, 1361-1371. Alexander, A., Smith, P. & Rosengren. (2009). Cannabinoids in the treatment of cancer. Cancer Leers, 285, 6-12.

Arseneault, L., Cannon, M., & Wion, J. Causal associaon between Cannabis and psychosis: examinaon of the evidence. Brish Journal of Davidson, E., Vlachojannis, J., Cameron, M. & Chrubasik, S. (2013). Best available evidence in Cochrane reviews on herbal medicine? Evidence-Based Complementary Psychiatry, 184, 110-117 and Alternave Medicine, 1-7. Baker, D., Pryce, G., & Croxford, J. (2000). Cannabinoids control spascity and tremor in mulple sclerosis model. Nature, 404, 84-87. Elvin-Lewis, M. (2001). Should we be concerned about herbal remedies. Journal of Ethnopharmacology, 75, 141-164. Botswick, J. (2012). Blurred boundaries: the therapeucs and polics of medical marijuana. Mayo Clinical Proceedings, 87(2), 172-186.

Lewis, W., & Elvin-Lewis, M. (2003). Medical : Plants Affecng Human Health. New York: John Wiley. Callaghan R, Allebeck P, Sidorchuk A. (2013). Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes Control, 10, 1811-1820.

Glisson, J. & Walker, L. (2010). How physicians should evaluate dietary supplements. The American Journal of Medicine, 123(7), 577-582. Croxford, L. & Yamamura, T. (2005). Cannabinoids and the immune system: Potenal for the treatment of inflammatory diseases? Journal of Neuroimmunology, 166, 3-18. Herbert-Ashton, M. (2002). Geng a handle on herbals. TNT, 16-23. Green, A., & De-Vries, K. (2010). Cannabis use in palliave care-an examinaon of the evidence and the implicaon for nurse. Journal of Clinical Nursing, 19, 2454-2462. Kahn, I. (2006). Issues related to botanicals. Life Sciences, 78, 2033-2038. Grotenhermen, F. & Muller-Vahl, K. (2012). The therapeuc potenal of Cannabis and Cannabinoids, Deutsches Ärztebla Internaonal. Park, B., Cho, J., Kim, Y., Ahn, Y., & Son, C. (2012). A prospecve study on the safety of herbal medicines, used alone or with convenonal medicines. Journal of 109(29-30), 495-501. Ethnopharmocology, 143, 884-888. Hall, W., & Degenhardt, L. (2009). Adverse health effects of non- use. Lancet, 374, 1383-1391. Posadzki, P., Watson, L. & Ernst, E. (2013). Adverse effects of herbal medicines: an overview of systemac reviews. Clinical Medicine, 13(1), 7-12.

Tarn, D., Paterni, D., Good, J., Coulter, I., Galliher, J., Kravitz, R., Karlamangla, A. & Wenger, N. (2013). Physician-paent communicaon about dietary supplements. Paent Educaon and Counseling, 91, 287-294.

Resources Resources Cannabis: Psychedelics: Holland, J. (2010). The Pot Book: A Complete Guide to Cannabis. Its Role in Medicine, Polics, Science, and Culture. Vermont, Park Street. Alper, K., Lotsof, H., Frenken, G., Luciano, D. & Basaans. (1999). Treatment of acute opioid withdrawal with Ibogaine. The American Journal on Leung, L. (2011). Cannabis and its derivaves: Review of medical use. JABFM, 24(4), 452-462. Addicons, 8(3), 234-242. McLaren, J., Swi, W., Dillon, P. & Allsop, S. (2008). Cannabis potency and contaminaon: a review of the literature. Addicon, 103, 1100-1109. Grob, C., Danforth, A., Chopra, G., Hagerty, M., McKay, C., Halberstadt, A., & Greer, G. (2011). Pilot study of Psilocybin treatment for anxiety in paents with advanced-stage cancer. Arch. Gen. Psychiatry, 68(1), 71-78. McQuay, H. (2010). More evidence Cannabis can help in neuropathic pain. CMAJ, 182(14), 1494-1495. Krebs, Teri & Johansen, P. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Pletcher, M., Vinghoff, E., Kalhan, R., Richman, J., Safford, M., Sidney, S., Lin, F., & Kertesz, S. (2012). Associaon between marijuana exposure and Psychopharmacology, 26(7), 994-1002. pulmonary funcon over 20 years. JAMA, 307(2), 173-181. Nu, D. (2007). The development of a raonal scale to assess the harm of drugs and potenal misuse. The Lancet, 369, 1047-1053. Rahavashisth, T., Shaheen, M., Norris, K., Pan, D., Sinha, S., Ortega, J., & Friedman, T. (2012). Decreased prevalence of diabetes in marijuana users: cross-seconal data from the Naonal Health and Nutrion Examinaon Survey (NHANES) III. BMJ Open, 2, 1-9. Preva-Smith, K. & Prisinzano, T. (2010). New therapeuc potenal for psychoacve natural products. Natural Product Reports, 27, 23-31. Schreiner, A, Dunn M. (2012) Residual effects of cannabis use on neurocognive performance aer prolonged absnence: a meta-analysis. Exp Clin Prisinzano, T. (2009). Natural products as tools for neuroscience: Discovery and development of novel agents to treat drug abuse. Journal of Psychpharmacol, 20,420-429. Natural Products, 72, 581-587. Sco, K., Shah, S., Dalgleish, A. & Liu, W. (2013) Enhancing the acvity of Cannabidiol and other cannabinoids In vitro through modificaons to drug Ross, S. (2011) Serotonergic hallucinogens and emerging targets for addicon pharmacotherapies. Psychiatr. Clin. N. Am., 35, 357-374. combinaons and treatment schedules. Ancancer Research, 33(10), 4373-4380. Schultes, R., Hoffman, A. & Ratsch, C. (1992). Plants of the Gods. Their Sacred, Healing, and Hallucinogenic Powers. Vermont: Healing Arts. Tait, R, Mackinnon, A, Christensen H. (2011) Cannabis use and cognive funcon: 8-year trajectory in a young adult cohort. Addicon, 106, Sessa, B. (2012). The Psychedelic Renaissance. London: Musmell Hill. 2195-2203. Sewell, R., Halpern, J. & Pope, H. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 27(66), 1920-1922. Wilsey, B., Marcoe, T., Deutsch, R., Gouaux, B., & Sakai, S. (2013). Low-dose vaporized Cannabis significantly improves neuropathic pain. The Journal of Pain, 14(2), 136-148.

Resources Resources Legal Highs: Poisonous herbals and management: Evren, C. & Bozkurt, M. (2013). Synthec Cannabinoids: Crisis of the decade. The Journal Das, R., Parajuli, S., & Jayakumar, J. (2007). Last supper with mushroom soup: a case report of amatoxin poisoning. McGill Journal of Medicine, 10(2), 93-95. of Psychiatry and Neurological Sciences, 26, 1-11. Gresham, C., and Wilbeck, J. (2011). Toxicology in the emergency department: a review for the advanced pracce nurse. Advanced Emergency Jerry, J., Collins, G., & Streem, D. (2012). Synthec legal intoxicang drugs: The emerging Nursing Journal, 34(1), 43-54. ‘incense’ and ‘bath salt’ phenomenon. Cleveland Clinic Journal of Medicine, 79(4), Leathem, A., Dorran, T. (2007). Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies. CJEM, 9(2), 127-130. 258-264. Lippinco’s Manual of Toxicology. (2012). Lippinco, Williams & Wilcons.

Zawilska, J.B. (2011). “Legal highs”-New players in the old drama. Current drug abuse Lewis, W., & Elvin-Lewis, M. (2003). Medical Botany: Plants Affecng Human Health. New York: John Wiley. reviews, 4, 122-130 Nelson, L., Lewin, N., Howland, M. Hoffman, R., Goldfrank, L. & Flomenbaun, N. (2010). Goldfrank’s Toxicologic Emergencies, 9th Ed. New York: McGraw-Hill

Perduri, R., Gobbs, S. (2009). Unexpected aflatoxin exposure in a women in Northern Italy: a case report. Cases Journal, 2, 7736.

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